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Curcumin interferes with chitin synthesis in Aedes aegypti: a computational and experimental investigation

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Abstract

Throughout history, vector-borne diseases have consistently posed significant challenges to human health. Among the strategies for vector control, chemical insecticides have seen widespread use since their inception. Nevertheless, their effectiveness is continually undermined by the steady growth of insecticide resistance within these vector populations. As such, the demand for more robust, efficient, and cost-effective natural insecticides has become increasingly pressing. One promising avenue of research focuses on chitin, a crucial structural component of mosquitoes' exoskeletons and other insects. Chitin not only provides protection and rigidity but also lends flexibility to the insect body. It undergoes substantial transformations during insect molting, a process known as ecdysis. Crucially, the production of chitin is facilitated by an enzyme known as chitin synthase, making it an attractive target for potential novel insecticides. Our recent study delved into the impacts of curcumin, a natural derivative of turmeric, on chitin synthesis and larval development in Aedes aegypti, a mosquito species known to transmit dengue and yellow fever. Our findings demonstrate that even sub-lethal amounts of curcumin can significantly reduce overall chitin content and disrupt the cuticle development in the 4th instar larvae of Aedes aegypti. Further to this, we utilized computational analyses to investigate how curcumin interacts with chitin synthase. Techniques such as molecular docking, pharmacophore feature mapping, and molecular dynamics (MD) simulations helped to illustrate that curcumin binds to the same site as polyoxin D, a recognized inhibitor of chitin synthase. These findings point to curcumin's potential as a natural, bioactive larvicide that targets chitin synthase in mosquitoes and potentially other insects.

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Acknowledgements

All authors acknowledge the support provided by Department of Biochemistry and Forensic Science and the Department of Microbiology and Biotechnology (DST-FIST supported department). Author, P.R is thankful to ScHeme Of Developing High quality research (SHODH), Education department, Government of Gujarat, India for providing student support fellowship. Special thanks is extended to Dr. Rajendra Ku. Baharia, of ICMR-National Institute of Malaria Research (NIMR) Field Unit (FU), Nadiad, Gujarat for providing Aedes aegypti specie used for the experiments. All authors would like to thank Department of Chemistry and Department of Botany, Bioinformatics and Climate Change Impacts Management, School of Sciences at Gujarat University for allowing access to the advance instrumentation and the bioinformatics research facilities.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for profit sectors.

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Authors and Affiliations

  1. Department of Biochemistry & Forensic Science, University School of Sciences, Gujarat University, Ahmedabad, Gujarat, 380009, India

    Priyashi Rao, Jinal Ninama, Mansi Dudhat & Rakesh M. Rawal

  2. Department of Life Science, University School of Sciences, Gujarat University, Ahmedabad, Gujarat, 380009, India

    Rakesh M. Rawal

  3. Department of Microbiology & Biotechnology, University School of Sciences, Gujarat University, Ahmedabad, Gujarat, 380009, India

    Dweipayan Goswami

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  1. Priyashi Rao
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PR and DG wrote the manuscript; PR, JN and MD performed experiments; PR prepared figures, and tables; RMR conceptualized the idea; RMR and DG critically proofread the manuscript.

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Correspondence to Rakesh M. Rawal.

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Rao, P., Ninama, J., Dudhat, M. et al. Curcumin interferes with chitin synthesis in Aedes aegypti: a computational and experimental investigation. Mol Divers (2023). https://doi.org/10.1007/s11030-023-10672-0

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